Publications by authors named "Theodoros G Soldatos"

Recent developments on artificial intelligence (AI) and machine learning (ML) techniques are expected to have significant impact on public health in several ways. Indeed, modern AI/ML methods have been applied on multiple occasions on topics ranging from drug discovery and disease diagnostics to personalized medicine, medical imaging, and healthcare operations. While such developments may improve several quality-of-life aspects (such as access to health services and education), it is important considering that some individuals may face more challenges, particularly in extreme or emergency situations.

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  • - The fight against COVID-19 requires understanding the complex relationship between the disease’s diverse symptoms and the underlying molecular mechanisms of the SARS-CoV-2 virus, which is crucial for developing effective treatments.
  • - Researchers created a comprehensive knowledge model by compiling existing data, which has been validated through recent findings, indicating the model's usefulness in generating and testing new hypotheses related to COVID-19.
  • - The model is accessible via the "COVID-19 Explorer" webserver and aims to provide insights across different organ systems, potentially leading to the discovery of new drug candidates and biomarkers to enhance therapeutic strategies.
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  • The COVID-19 pandemic, beginning in early 2020, has caused over half a billion infections and 6 million deaths, highlighting a fragmented understanding of the disease's diverse symptoms and mechanisms.
  • Despite vaccines being available, effective treatments for severe cases are still urgently needed, especially with new variants emerging, due to COVID-19's complex effects on various body tissues and organs.
  • Utilizing the Dataome platform, researchers created an integrated model linking COVID-19 symptoms to molecular behavior and intercellular communication, which can aid in drug development and risk factor identification, all of which is accessible through the open-source COVID-19 Explorer.
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  • Immunotherapy has become essential in cancer treatment, with drugs like ipilimumab, nivolumab, and pembrolizumab targeting CTLA-4 and PD-1 to enhance T-cell activation, but this can cause serious side effects like colitis.
  • The research explores how the different mechanisms of action between anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab, pembrolizumab) drugs influence the occurrence and severity of colitis using data from the FDA's Adverse Event Reporting System.
  • Findings indicate that ipilimumab is linked to a significantly higher incidence of colitis compared to anti-PD-1 drugs, though the anticipated molecular mechanisms behind this
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  • Many drug development efforts fail due to unexpected negative reactions, highlighting the need for better safety analysis methods.
  • This work reviews quantitative methods for analyzing adverse events and suggests enhancing these methods with molecular data to gain deeper insights.
  • Incorporating molecular data can improve understanding of drug safety, support better clinical trial designs, and utilize advanced techniques like machine learning for public health benefits.
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Adverse drug reactions (ADRs) of targeted therapy drugs (TTDs) are frequently unexpected and long-term toxicities detract from exceptional efficacy of new TTDs. In this proof-of-concept study, we explored how molecular causation involved in trastuzumab-induced cardiotoxicity changes when trastuzumab was given in combination with doxorubicin, tamoxifen, paroxetine, or lapatinib. The data analytical platform Molecular Health Effect was utilized to map population ADR data from the US Food and Drug Administration (FDA) Adverse Event Reporting System to chemical and biological databases (such as UniProt and Reactome), for hypothesis generation regarding the underlying molecular mechanisms causing cardiotoxicity.

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  • A new pharmacological model was developed to enhance the prediction of adverse events (AEs) in FDA drug labels during drug approval, using a larger dataset and an improved algorithm.
  • * The model evaluates comparator drugs with similar target activities by analyzing data from the FDA Adverse Event Reporting System (FAERS), drug labels, and medical literature.
  • * The enhanced model demonstrates strong performance metrics, with an F1 score of 0.71 and areas under the precision-recall and receiver operating characteristic curves of 0.78 and 0.87, respectively, indicating its effectiveness in predicting AEs.
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  • The study evaluates a new computational tool, MH BRCA, for classifying genetic variants in hereditary breast and/or ovarian cancer (HBOC), demonstrating a high accuracy in identifying pathogenic variants.
  • The tool showed a 99.98% agreement with existing classification databases, significantly reducing uncertainty in variant interpretation and identifying several cases with potential family risks for HBOC.
  • The findings also suggest a strong link between the classification of variants and their predicted efficacy in PARP inhibitor treatment, underscoring the importance of accurate variant assessment in clinical settings.
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Immune checkpoint inhibition represents an important therapeutic option for advanced melanoma patients. Results from clinical studies have shown that treatment with the inhibitors Pembrolizumab and Nivolumab provides improved response and survival rates. Moreover, combining Nivolumab with the inhibitor Ipilimumab is superior to the respective monotherapies.

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The development of monoclonal antibodies has dramatically changed the outcome of patients with non-Hodgkin's lymphoma (NHL), the most common hematological malignancy. However, despite the satisfying results of monoclonal antibody treatment, only few NHL patients are permanently cured with single-agent therapies. In this context, radioimmunotherapy, the administration of radionuclides conjugated to monoclonal antibodies, is aimed to augment the single-agent efficacy of immunotherapy in order to deliver targeted radiation to tumors, particularly CD20+ B-cell lymphomas.

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  • Molecular characterization of tumors helps oncologists make better treatment decisions, but genomic medicine is still developing, leaving early adopters to take on most risks.
  • Innovative precision oncology trials have emerged globally to prove the effectiveness of predictive biomarkers and analytics to improve patient outcomes.
  • As more data on clinico-molecular outcomes is collected, we anticipate a shift from expert systems to AI-assisted treatment decision support, which could greatly enhance cancer care.
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  • * This study analyzed data from the FDA Adverse Event Reporting System involving approximately 1500 prostate cancer patients to identify side effects associated with radium-223 dichloride, noting that hematological reactions were common.
  • * The research highlights the need for more prospective studies to better understand radium-223 dichloride's safety, marking an initial effort to evaluate its safety profile based on real-world data.
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  • Adverse events from therapeutic interventions are common but often unavoidable, providing data to study the link between human traits and drug-induced changes.
  • Understanding the molecular basis of these adverse events can lead to safer drugs and help identify new biomarkers and treatment targets.
  • The analysis of adverse events from the FAERS database revealed that many patients experience drug interactions, underlining the need for better optimization of co-medication therapies.
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  • A new method is introduced for analyzing how drugs affect clinical phenotypes by integrating data from 8.2 million clinical reports on drug side effects with drug-target molecular information.
  • This approach has yielded 1.8 million connections between clinical phenotypes and 770 drug-targets, creating a comprehensive reference for human-targets and enabling rapid hypothesis testing.
  • The validation showcases its practical applications in predicting drug safety and designing effective combination therapies, leveraging extensive clinical data available in healthcare settings.
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  • * Immunotherapy with these agents can lead to increased toxicity and immune-related side effects, although the exact mechanisms behind these issues are not well understood.
  • * A retrospective analysis of nearly 7,700 melanoma patients shows that reactions are specifically linked to the use of ipilimumab and nivolumab, with combined treatment presenting a combination of side effects from both drugs.
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Case reports suggest an association between second-generation antipsychotics (SGAs) and serotonin syndrome (SS). The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) was analyzed to generate hypotheses about how SGAs may interact with pharmacological targets associated with SS. FAERS was integrated with additional sources to link information about adverse events with drugs and targets.

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As the amount of genome information increases rapidly, there is a correspondingly greater need for methods that provide accurate and automated annotation of gene function. For example, many high-throughput technologies--e.g.

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The third Heidelberg Unseminars in Bioinformatics (HUB) was held on 18th October 2012, at Heidelberg University, Germany. HUB brought together around 40 bioinformaticians from academia and industry to discuss the 'Biggest Challenges in Bioinformatics' in a 'World Café' style event.

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Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth.

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Background: Keeping up-to-date with bioscience literature is becoming increasingly challenging. Several recent methods help meet this challenge by allowing literature search to be launched based on lists of abstracts that the user judges to be 'interesting'. Some methods go further by allowing the user to provide a second input set of 'uninteresting' abstracts; these two input sets are then used to search and rank literature by relevance.

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Understanding complex systems often requires a bottom-up analysis towards a systems biology approach. The need to investigate a system, not only as individual components but as a whole, emerges. This can be done by examining the elementary constituents individually and then how these are connected.

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The quantities of data obtained by the new high-throughput technologies, such as microarrays or ChIP-Chip arrays, and the large-scale OMICS-approaches, such as genomics, proteomics and transcriptomics, are becoming vast. Sequencing technologies become cheaper and easier to use and, thus, large-scale evolutionary studies towards the origins of life for all species and their evolution becomes more and more challenging. Databases holding information about how data are related and how they are hierarchically organized expand rapidly.

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Background: Biological knowledge is represented in scientific literature that often describes the function of genes/proteins (bioentities) in terms of their interactions (biointeractions). Such bioentities are often related to biological concepts of interest that are specific of a determined research field. Therefore, the study of the current literature about a selected topic deposited in public databases, facilitates the generation of novel hypotheses associating a set of bioentities to a common context.

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Life scientists are often interested to compare two gene sets to gain insight into differences between two distinct, but related, phenotypes or conditions. Several tools have been developed for comparing gene sets, most of which find Gene Ontology (GO) terms that are significantly over-represented in one gene set. However, such tools often return GO terms that are too generic or too few to be informative.

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Background: Complexity is a key problem when visualizing biological networks; as the number of entities increases, most graphical views become incomprehensible. Our goal is to enable many thousands of entities to be visualized meaningfully and with high performance.

Results: We present a new visualization tool, Arena3D, which introduces a new concept of staggered layers in 3D space.

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